Folding/unfolding of mechanical proteins, binding/unbinding of non-covalently attached biomolecules, and selectivity of biological transmembrane ion channels are at the heart of many important processes like muscle stretching, immune response, electrical signaling, and are the target of experimental and theoretical investigations. Dr. Schulten proposes to use Steered Molecular Dynamics (SMD) simulations, a tool that allows one to investigate processes which cannot be easily detected in experiments, to: 1) understand how the architecture of sandwich domains in the immunoglobulin (Ig) and fibronectin type III (FnIII) domains of titin has served nature to design proteins which can withstand high forces and act as stress sensors, and resolve at the atomic level the mechanical stretching and unfolding of protein domains by forced unfolding of the Ig and FnIII domains; 2) quantify changes in the protein flexibility connected with antibody maturation and investigate hapten interactions with residues of the binding pocket by inducing the unbinding of the hapten; 3) determine the potential of mean force and explain the basis for the fidelity with which the K+ channel distinguishes between K+ and Na+ ions, and for the selectivity encoded in the signature sequence of the K+ channel by simulating the passing of K+ ions through the channel. These studies will provide results that can be directly compared to experimental data, as well as complement observations through atomic-level details of these processes explaining the data.